Methods and kits to treat chronic inflammatory immune diseases by administering a proteasome inhibitor and an interleukin 2 receptor agonist

• US 20070098685A1
• Filed: 01/19/2006
• Published: 05/03/2007
• Est. Priority Date: 01/19/2005
• Status: Abandoned Application

• Current Assignee: Stephen Brand
• Original Assignee: Stephen Brand
• Inventors: Brand, Stephen
• Application Number:
  US11/335,445
• Publication Number:
  US 20070098685A1
• Time in Patent Office: Days
• US Class Current: 424/85.2
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/69 Boron compounds
• CPC Class Codes: A61K 38/05 Dipeptides
• CPC Class Codes: A61K 38/2013 IL-2
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca

Abstract

Methods and kits for treatment of immune diseases with an IL2 receptor agonist and a proteasome inhibitor are provided.

Claims

1. A method of treating a mammal suffering from an immune condition, comprising administering to the mammal a course of treatment comprising a combination of an interleukin 2 receptor agonist and a proteasome inhibitor.

2. The method of claim 1, wherein administering to the mammal further comprises measuring remission of the immune condition in the absence of continuous treatment.

3. The method of claim 2, wherein remission of the immune condition in the absence of continuous treatment comprises at least 0.2% of an average lifespan of said mammal.

4. The method of claim 1, wherein the mammal is a human.

5. The method of claim 1, wherein the immune condition is selected from:

rheumatoid arthritis, Crohn'"'"'s disease, multiple sclerosis, psoriasis, and Type I diabetes.

6. The method of claim 1, wherein the immune condition is immune rejection of a transplanted allogenic graft of organ or tissue.

7. The method of claim 1, wherein the course of treatment comprises a period of time less than 6 months.

8. The method of claim 1, wherein the administering is delivering by a route that is systemic.

9. The method of claim 8, wherein the route of systemic administering is at least one of:

oral, subcutaneous, intramuscular and intravenous.

10. The method of claim 1, wherein administering the combination is administering the agonist and the inhibitor sequentially.

11. The method of claim 1, wherein the treatment is administering doses of the agonist and the inhibitor at different frequencies.

12. The method of claim 11, wherein administering the agonist is more frequent than administering the inhibitor.

13. The method of claim 1 wherein the agonist is human recombinant interleukin 2.

14. The method of claim 13 wherein the human recombinant interleukin 2 is Proleukin™

des ala-1 serine 125 human interleukin 2.

15. The method of claim 13 wherein the dose of interleukin 2 receptor agonist the mammal is less than 20 million units.

16. The method of claim 13 wherein the dose of interleukin 2 receptor agonist to the mammal is less than 7 million units.

17. The method of claim 1, wherein the inhibitor is a peptide boronic acid.

18. The method of claim 17 wherein the peptide boronic acid is PS-341 (Velcade™

), Pyz Phe boro leu;

Pyz2,5 pyraninecarboxylic acid.

19. The method of claim 18, wherein the dose of the PS-341 is less than 1 mg per m² of the mammal.

20. The method of claim 1, wherein the course of treatment is administering the inhibitor on days 1, 5, 9 and 13 of a 21 day cycle.

21. A use of a combination of a proteasome inhibitor and an interleukin 2 receptor agonist to induce apoptosis selectively in pathogenic CD4⁺ Th1 T cells.

22. The use of claim 21, further comprising measuring inhibiting NFκ

B activation and the increasing c-myc and p53 acting in synergy together or in pairs, and measuring initiating pro-apoptotic changes in a plurality apoptosis control proteins.

23. The use of claim 22, further comprising measuring enhancement of apoptotic potency by coordinated changes in the activity of multiple transcription factors controlling apoptosis through inhibiting common pathway of proteolysis, by a drug acting on a single defined molecular target, the proteasome.

24. A kit for treating an immune condition comprising a unit dose of each of an interleukin 2 receptor agonist, a proteasome inhibitor, and a container.

25. The kit of claim 24, comprising instructions for use.

26. The kit of claim 24, wherein the dose is contained in an infusion container.